1. Field of the Invention
This invention relates generally to methods of detecting the presence of a cervical carcinoma. Specifically, this invention relates to a method of detecting a cervical carcinoma by detecting the presence of a chromosome abnormality in a cervical cell that is associated with the cervical carcinoma.
2. Background Art
Cervical carcinomas are the second most common tumors in women worldwide. The tumor incidence shows strong variability, with industrialized countries having lower morbidity and mortality rates than do developing countries (Pisani et al. (1993) "Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden" Int J Cancer 55:891-903) which may be attributable to differences in cytologic screening programs (Hakama et al. (1986) "Screening for cancer of the uterine cervix" IARC Scientific Publications No. 76, Lyon, France). Although other factors, such as cigarette smoking, may influence the incidence of cervical cancer, infection with human papilloma virus (HPV) can be an initiating event for cervical carcinogenesis. (IARC Monograph, 1995). An HPV infection alone, however, is not sufficient for the progression of the disease from a stage of mild cellular dysplasia to a stage of invasive carcinoma since some HPV infected cervical cells may never progress to the more malignant stage, and in fact, may never progress past a stage of mild dysplasia. The traditional clinical diagnostic test for the presence of dysplastic cells, the Papanicolaou (Pap) smear, does not provide a reliable predictor of the progression of dysplastic cells to cancerous cells since this test is based upon morphological characteristics of the cells which do not reliably reflect the genetic state of the cells. Additionally, the Pap smear analysis is essentially a subjective test which is therefore susceptible to misinterpretation.
Polyploidy has been associated with the transition of normal cervical cells to dysplastic cervical cells, but this crude genetic determination has also not been associated with cells undergoing a transition past a stage of mild dysplasia other than showing a general increase in genetic instability. This genetic instability, as determined by monitoring ploidy levels, appears nonspecific to a particular chromosome and does not provide a correlation to the transition of dysplasia to invasive carcinoma. Therefore some additional process must occur for a transition of the dysplastic cervical cells to the more advances stages of the disease. It is conceivable that specific genetic aberrations are required for the multistep process of cervical cell tumor initiation and progression (Fearon et al. (1990) "A genetic model for colorectal carcinogenesis" Cell 61:759-767 and Zur Hausen, H. (1994) "Disrupted dichotomous intracellular control of human papilloma virus infection in cancer of the cervix" Lancet 343:955-957), but this association has never been discovered, and therefore, a relatively simple genetic determination of cervical cells in the more advanced stages of the disease, such as those entering into or already in the invasive stage, has not yet been possible.
Determination of mandatory genetic aberrations for tumor progression would lead to valuable diagnostic predictors. There is, therefore, a need for a method that can be used to readily detect the presence of a cancerous cervical cell that is independent of tests such as cytologic or morphologic appearance or overall ploidy levels.
The present invention solves this need by disclosing for the first time a method which allows the detection of a cancerous cervical cell by detecting a chromosome abnormality which is associated with a cervical carcinoma. Using this method, therefore, one can now detect the presence of a cancerous cervical cell in a population of cells which may be either HPV infected or polyploid, or both, and regardless of the morphological appearance of the cell or the cells ploidy level.